Gonorrhea is a major health problem world-wide. In the U.S. it is one of the ten most often reported infectious diseases according to the Center for Disease Control. The disease is caused by Neisseria gonorrheae, a gram-negative diplococcus. A major virulence factor is the pilus, a proteinaceous structure on the bacterial surface which allows the bacterium to attach to epithelial cells of the host. It is composed of repeating identical subunits of 18,000 daltons. To date nothing is known about the secondary, tertiary or quarternary structure of the pilus. The mode of attachment of pili to host cells is also not known. Antigenic variation of the pilus protein has hampered efforts to design a pilus-based vaccine. By using a combination of protein and DNA biochemistry and genetic approaches we will examine all these aspects of the N. gonorrheae pilus. Our data on the structure and function of the gonococcal pilus will shed light on other bacterial systems which also produce fimbriate structures which have homology to the pilus and which are thought to undergo antigenic variation.